Evidence mapPaperPMID 40617868Full record

ArticleCommunications biology2025

TTK activates ATR through RPA2 phosphorylation to promote olaparib resistance in ovarian cancer.

Gonghua Qi, Hanlin Ma, Jingying Chen, Panpan Gai, Kai Teng

Abstract read
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Gonghua QiDepartment of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
Hanlin MaDepartment of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
Jingying ChenDepartment of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.
Panpan GaiChinese People's Liberation Army, Laiyang, China.
Kai TengDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. tengkaitk@126.com.ORCID http://orcid.org/0000-0002-5782-1307

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82303896Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation) ZR2021QH020Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation) ZR2023QH306Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation) ZR2024MH293
6 · The paper itself

Abstract

Resistance to poly(ADP‒ribose) polymerase inhibitors (PARPis) remains a significant challenge in ovarian cancer (OC) treatment. TTK protein kinase (TTK) has been implicated in cisplatin resistance in OC, but its role in PARPi resistance remains unclear. In this research, we found that TTK inhibition overcome olaparib resistance in HR-proficient OC cells, whereas TTK promotes olaparib resistance in HR-deficient OC cells. Mechanistically, TTK directly interacts with RPA2, facilitating phosphorylation of its S33 residue to activate the ATR signaling pathway. Knocking down RPA2 increased olaparib sensitivity in OC cells. Additionally, TTK-mediated resistance to olaparib through the RPA2/ATR signaling pathway was confirmed via both in vitro and in vivo models. In conclusion, TTK inhibition overcomes olaparib resistance in HR-proficient OC cells, in part by suppressing RPA2-S33 phosphorylation and attenuating ATR signaling. TTK inhibitors offer a promising strategy to increase the therapeutic efficacy of PARPis in OC patients.

Indexed as

Ataxia Telangiectasia Mutated ProteinsCell Cycle ProteinsDrug Resistance, NeoplasmOvarian NeoplasmsPhthalazinesPiperazinesProtein Serine-Threonine KinasesReplication Protein AAnimalsCell Line, TumorFemaleHumansMiceMice, NudePhosphorylationPoly(ADP-ribose) Polymerase InhibitorsAtaxia Telangiectasia Mutated ProteinsATR protein, humanCell Cycle ProteinsolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsProtein Serine-Threonine KinasesReplication Protein ARPA2 protein, human

Identifiers

PMID40617868
PMCPMC12228772

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.